Related Experiment Video
Updated: Aug 12, 2025
En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative
Shigeru Kawade1, Kazuma Ogiso1, Sigfrid Casmir Shayo1
1Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
Aims/Introduction:
The mechanisms underlying the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet-induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)-induced endothelial dysfunction in high-fat diet (HFD)-induced obese mice.
Materials And Methods:
Mice were fed a control diet or high-fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments.
Results:
Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD-fed mice only under paired feeding but not under free feeding. Endothelial-dependent vasodilation under FFA exposure conditions was significantly lower in HFD-fed mice than in control diet-fed mice, and luseogliflozin treatment ameliorated FFA-induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD-induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA-induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA-induced endothelial dysfunction in HFD-fed mice.
Conclusions:
It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA-induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibition with luseogliflozin improved endothelial dysfunction in obese mice, particularly with caloric restriction. This effect is linked to increased antioxidant enzyme SOD2 and reduced oxidative stress.
Area of Science:
- Cardiovascular Research
- Metabolic Disease Research
- Pharmacology
Background:
- Diet-induced obesity is linked to aortic endothelial dysfunction.
- The precise mechanisms of SGLT2 inhibitors in this context remain unclear.
Purpose of the Study:
- To investigate if SGLT2 inhibition by luseogliflozin ameliorates free fatty acid (FFA)-induced endothelial dysfunction in high-fat diet (HFD)-induced obese mice.
- To explore the role of caloric restriction in the efficacy of luseogliflozin.
Main Methods:
- Mice were fed high-fat or control diets, with or without luseogliflozin, under free or paired feeding conditions.
- Thoracic aortas were analyzed for endothelial function, oxidative stress markers, and antioxidant enzyme expression.
Main Results:
- Luseogliflozin improved metabolic parameters and endothelial function in HFD mice, but only under paired feeding (caloric restriction).
- Luseogliflozin treatment reduced FFA-induced reactive oxygen species (ROS) production and increased superoxide dismutase 2 (SOD2) expression.
- SOD2 activity reversed FFA-induced endothelial dysfunction in HFD mice.
Conclusions:
- Caloric restriction is crucial for luseogliflozin's beneficial effects on metabolic parameters and endothelial function.
- SGLT2 inhibition may improve FFA-induced endothelial dysfunction by enhancing SOD2 expression and reducing ROS production in the aorta.
